Detection of cancer in the dense breast is a significant challenge for x-ray mammography. Similarities between the density of lesions and surrounding breast tissue, in addition to x-ray opacity, limit effective detection of small to medium sized tumors in these patients. To address this concern, nuclear medicine-based imaging techniques, such as positron emission tomography (PET) used with 18F-Fluorodeoxyglucose (FDG), have been applied with some success to breast imaging. These methods rely upon differences in metabolic activity between tumor and normal tissue, instead of density contrasts for creating images. Although these techniques have demonstrated some potential in detecting breast lesions in dense breasts, their limited spatial resolution and specificity does not warrant their sole use for making diagnoses. The most effective method for diagnosis remains histological evaluation of tissue samples acquired from biopsy. In many cases stereotactic core biopsy of suspicious lesions guided by x-ray mammography is an effective and minimally-invasive method for performing these procedures. In the case of lesions optimally detected in a dense breast with PET, however, x-ray techniques may not be optimal for biopsy guidance. In response to this need, we propose the construction of a device that will be capable of acquiring high resolution images of the breast using PET techniques. These images will then be used to assess radiotracer uptake and guide the placement of a biopsy needle into suspicious lesions. Image-based verification of needle positioning will be accomplished by acquiring a set of stereotactic planar, positron emission mammography (PEM) images. This dual modality system called, PEM-PET, will be capable of performing three main tasks: lesion detection, radiotracer quantitation and lesion localization. The apparatus will consist of two sets of rotating, large-area planar pixelated scintillator arrays. The use of rotating planar detectors was adopted (instead of the more intuitive ring geometry) to facilitate access to the breast during biopsy procedures, while permitting acquisition of PEM and PET images. The choices of scintillator material (Lutetium Oxyorthosilicate) and detector pixel size were based on computer simulation studies and model observer studies. Development of the system will include the construction of the detector units, and the creation of tomopraphic and planar image reconstruction methods. The PEM-PET system will be optimized and evaluated with task-dependent metrics obtained from model and human observer studies, and a pre-clincal trial. At the completion of this project an apparatus for the effective detection and diagnosis of lesions for use in the subgroup of women with difficult to image breasts will have been developed and evaluated.